Multifunctional Flame-Retardant Melamine-Based Hybrid Foam for Infrared Stealth, Thermal Insulation, and Electromagnetic Interference Shielding.

Multifunctionalization is an important development direction of electromagnetic interference (EMI)-shielding materials. However, it is still a huge challenge to effectively integrate multiple functions into materials. Herein, we reported a facile method to fabricate multifunctional EMI-shielding materials, which were assembled with multidimensional components consisting of a 3D melamine-formaldehyde (MF) foam skeleton, 0D ferroferric oxide (Fe3O4) nanoparticles, and 1D silver nanowires (AgNWs) via coprecipitation and dip-coating processes. Due to the coaction of conductive AgNWs and magnetic Fe3O4 nanoparticles, the resultant hybrid foam showed excellent absorption-dominant EMI-shielding performances with a high specific EMI-shielding effectiveness value of 12,704 dB cm2 g-1. Moreover, thanks to the multilayer porous micro-/nanostructure and the nonflammability of functional coatings, the hybrid foam shows excellent flame retardancy and heat insulation, making it attractive for the functions of infrared stealth and heat insulation. The corresponding mechanism is discussed in detail. Combined with the advantages of high thermal insulation, flame retardancy, elasticity, and excellent absorption-dominant EMI-shielding performances, the hybrid foam showed great applications in the fields of both military and civilian. This work provides new inspiration and insights for the design of multifunctional high-performance EMI-absorbing materials.

Multifunctional Photothermal Conversion Nanocoatings Toward Highly Efficient and Safe High-Viscosity Oil Cleanup Absorption.

Efficient and safe cleanup for the high-viscosity heavy oil spill has been a worldwide challenge due to its sluggish flowability, while classic absorption methods by electric/solar heating are seriously limited by low efficiency and high fire hazards during heating of highly flammable oil. Facing this dilemma, we reported a novel flame-retardant photothermal conversion nanocoating to endow commercial foams with highly efficient and safe heavy oil cleanup absorption. This multifunctional nanocoating consisting of nano-Fe3O4 and reduced graphene oxide (rGO) that both showed photothermal conversion ability and non-flammable nature can be firmly deposited on the polymer foam skeletons via facile coprecipitation and dip-coating processes. The composite foam showed a tough morphology with high hydrophobicity and low density, thus leading to selective high absorption for various oils and organic solvents. Due to the double photothermal conversion effects of nano-Fe3O4 and rGO, the temperature of the foam can be rapidly heated at a rate of ∼103.5 °C/min (the fastest rate ever) under 1 sun irradiation. Consequently, the foam with a high absorption capacity of 75.1 times its weight demonstrated a rapid absorption rate of 9000 g m-2 min-1 for large-viscosity oil under 1 sun irradiation, which was 3 times faster than previously reported. Furthermore, benefitting from high flame retardancy, elasticity, and magnetism, the foam can be safely and repeatedly used for magnetically controllable oil cleanup absorption, which effectively avoids oil spill hazards.

Phenotype Regulation of Smooth Muscle Cells Through Facial Crystallization of Poly(ɛ-Caprolactone).

Phenotype conversion of smooth muscle cells (SMCs) plays a key role in the formation of atherosclerosis. Understanding how SMCs respond to a micro/nano-topology and elucidating the cellular mechanism of phenotype conversion is critical to the atherosclerosis treatment. Herein, we prepared poly(ɛ-caprolactone) (PCL) spherulites with a radius more than 350 µm for the studying of radial microstructure influence on SMCs behaviors. We found that on the PCL spherulitic films, SMCs grew aligning the radial direction of PCL spherulites, overexpressed α-SMA gene than OPN gene, and preferred contractile phenotype. FAK signaling pathway and ROCK1 signaling pathway both contributed to the contractile phenotype maintenance of SMCs. This work illustrated the feasibility of spherulites in regulating SMCs behaviors, and elucidated the mechanism how SMCs respond to a radial micro/nano-topology. This research may provide theoretical basis for the atherosclerosis formation and treatment.

Integration of Cell-Penetrating Peptides with Rod-like Bionanoparticles: Virus-Inspired Gene-Silencing Technology.

Inspired by the high gene transfer efficiency of viral vectors and to avoid side effects, we present here a 1D rod-like gene-silencing vector based on a plant virus. By decorating the transacting activator of transduction (TAT) peptide on the exterior surface, the TAT-modified tobacco mosaic virus (TMV) achieves a tunable isoelectric point (from ∼3.5 to ∼9.6) depending on the TAT dose. In addition to enhanced cell internalization, this plant virus-based vector (TMV-TAT) acquired endo/lysosomal escape capacity without inducing lysosomal damage, resulting in both high efficiency and low cytotoxicity. By loading silencer green fluorescent protein (GFP) siRNA onto the TMV-TAT vector (siRNA@TMV-TAT) and interfering with GFP-expressing mouse epidermal stem cells (ESCs/GFP) in vitro, the proportion of GFP-positive cells could be knocked down to levels even lower than 15% at a concentration of ∼100% cell viability. Moreover, by interfering with GFP-expressing highly metastatic hepatocellular carcinoma (MHCC97-H/GFP) tumors in vivo, treatment with siRNA@TMV-TAT complexes for 10 days achieved a GFP-negative rate as high as 80.8%. This work combines the high efficiency of viral vectors and the safety of nonviral vectors and may provide a promising strategy for gene-silencing technology.

Tuning Alginate-Gelatin Bioink Properties by Varying Solvent and Their Impact on Stem Cell Behavior.

Bioink optimization is considered as one of main challenges in cell-laden 3D bioprinting. Alginate-Gelatin (Alg-Gel) hydrogel have been extensively used as bioink. However, its properties could be influenced by various parameters, and little is known about the evidence featuring the impact of solvent. Here we investigated four Alg-Gel bioink by varying solvent ionic strength (named B-1, B-2, B-3 and B-4). Mechanical properties and printability of bioink samples and their impacts on behaviors of encapsulated epidermal stem cells (ESCs) were tested. Bioink with increased ionic strength of solvent showed decreased stiffness and viscosity, and increased swelling and degradation by printability and mechanical property tests. Due to the increased swelling and degradation was associated with shape-maintenance of post-printing constructs, B-3 and B-4 were hardly observable after 14 days. Cellular behaviors were assessed through viability, proliferation, aggregation and differentiation tests. B-2 with optimal properties resulted in higher viability and proliferation of ESCs, and further facilitated cellular aggregation and lineage differentiation. We demonstrated that the solvent can be tuned by ionic strength to control the properties of Alg-Gel bioink and post-printing constructs, which represented a promising avenue for promotion of therapeutic stem cell behaviors in 3D bioprinting.

Balancing antimicrobial activity with biological safety: bifunctional chitosan derivative for the repair of wounds with Gram-positive bacterial infections.

Infection control and the promotion of healing are two key factors during the wound repair process. However, it is still a major challenge for one material to inhibit bacterial growth efficiently and promote wound healing at the same time. Here, a bifunctional chitosan derivative (CS-G/mPEG) was prepared by the successive modification of chitosan with carboxymethoxypolyethylene glycol (mPEG-COOH) and aminoiminomethanesulfonic acid (AIMSOA). We demonstrated that CS-G/mPEG can selectively disrupt bacterial membranes with high efficiency and thus kill Gram-positive bacteria without inducing hemolysis or cytotoxicity. In rats with full-thickness skin wounds infected with Staphylococcus aureus bacteria, CS-G/mPEG inhibited the growth of the bacteria and accelerated the healing of the wounds. Owing to the balance between the antimicrobial activity and biological safety of CS-G/mPEG, this bifunctional chitosan derivative is promising as an ideal anti-infective wound-repairing material for managing wounds with Gram-positive bacterial infections.

[Effect of aging on proliferative and differentiation capacity of human periodontal ligament stem cells].

OBJECTIVE: To evaluate the effect of aging on the proliferative and differentiation capacity of human periodontal ligament stem cells (PDLSCs). METHODS: Human periodontal ligament tissues were obtained from surgically extracted third molars from 6 subjects aged 18-20 years (group A) and 6 subjects aged 45-50 years (group B). The proliferative capacity of PDLSCs isolated from the tissues was examined with MTT assay, and the osteogenic and adipogenic differentiation capacity of the cells were evaluated using alizarin red staining and oil red O staining. SA-ßG expression was analyzed to assess the cell senescence. In both groups, PDLSCs were induced for osteogenic differentiation for 7 days, and the differentiation ability of the cells was assessed by examining alkaline phosphatase (ALP) activity and by detecting the expressions of osteocalcin (OCN) and ALP using Western blotting. RESULTS: Human PDLSCs were successfully isolated from the 12 teeth and were characterized as MSCs. The PDLSCs derived from donors of different ages were all capable of osteogenic and adipogenic differentiation, but their proliferative and osteogenic differentiation capacity decreased with the donors' age. The cells also exhibited an age- related increase in adipogenic differentiation capacity and SA-ßG expression. In both groups, the cells induced in osteogenic medium showed increased OCN expression and ALP activation, and the increments were more obvious in group A. CONCLUSION: Human PDLSCs can be isolated from periodontal ligament tissues even from donors of advanced ages, but their proliferative and differentiation capacity decreases and their adipogenic differentiation capacity increases with age.

Brain and muscle aryl hydrocarbon receptor nuclear translocator-like protein-1 cooperates with glycogen synthase kinase-3ß to regulate osteogenesis of bone-marrow mesenchymal stem cells in type 2 diabetes.

Type 2 diabetes mellitus (T2DM) is associated with inhibited osteogenesis of bone marrow mesenchymal stem cells (BMSCs). Brain and muscle ARNT-like protein 1 (BMAL1) has been linked to the T2DM-related bone remodeling, however, the specific mechanism is still unclear. Herein, we aimed to determine the role of BMAL1 in T2DM-induced suppression of BMSCs osteogenesis. Inhibited osteogenesis and BMAL1 expression were showed in diabetic BMSCs. And while ß-catenin and T cell factor (TCF) expression were decreased, the glycogen synthase kinase-3ß (GSK-3ß) and nemo-like kinase (NLK) expression were increased in diabetic BMSCs. Moreover, over-expression of BMAL1 led to recovered osteogenesis ability and activation of Wnt/ß-catenin pathway, which was partially due to inhibition of GSK-3ß caused by over-expression of BMAL1. Taken together, our findings provide new insights into the role of BMAL1 in T2DM-induced suppression of BMSCs osteogenesis. Over-expressed BMAL1 could recover BMSCs osteogenesis in T2DM partially by decreasing GSK-3ß expression to activate Wnt/ß-catenin pathway. BMAL1 may have a potential use in repairing diabetic bone metabolic disorders.

Communication between nitric oxide synthase and positively-charged surface and bone formation promotion.

Despite the effects on physiology of bone marrow mesenchymal stem cells (BMSCs) and bone tissue, biological signal communication between bone implants and them is seldom employed as a guidance to create an osteo-inductive interface. Herein, the positively-charged surface is constructed on bone implant from the perspective of mediation of nitric oxide synthase (NOS) expression to signal BMSCs osteo-differentiation. In vitro and in vivo results indicate that the proper surface potential on the positively-charged surface affects NOS to express a high level of inducible nitric oxide synthase (iNOS) in three NOS isoforms of the contacted BMSCs, upregulates their osteogenetic expression, and ultimately foster new bone growth. However, an excessively high surface potential produces substantial immunomodulatory effects thereby offsetting the aforementioned advantages. This study demonstrates that fine-tuning of the positively-charged surface and proper utilization of the communication between NOS and bone implants promote bone formation.

Influence of the intensity and loading time of direct current electric field on the directional migration of rat bone marrow mesenchymal stem cells.

Exogenic electric fields can effectively accelerate bone healing and remodeling through the enhanced migration of bone marrow mesenchymal stem cells (BMSCs) toward the injured area. This study aimed to determine the following: (1) the direction of rat BMSC (rBMSC) migration upon exposure to a direct current electric field (DCEF), (2) the optimal DCEF intensity and duration, and (3) the possible regulatory role of SDF-1/CXCR4 axis in rBMSC migration as induced by DCEF. Results showed that rBMSCs migrated to the positive electrode of the DCEF, and that the DCEF of 200 mV/mm for 4 h was found to be optimal in enhancing rBMSC migration. This DCEF strength and duration also upregulated the expression of osteoblastic genes, including ALP and OCN, and upregulated the expression of ALP and Runx2 proteins. Moreover, when CXCR4 was inhibited, rBMSC migration due to DCEF was partially blocked. These findings indicated that DCEF can effectively induce rBMSC migration. A DCEF of 200 mV/mm for 4 h was recommended because of its ability to promote rBMSC migration, proliferation, and osteogenic differentiation. The SDF-1/CXCR4 signaling pathway may play an important role in regulating the DCEF-induced migration of rBMSCs.

[Difference of in vitro osteogenic differentiation and osteoclast capacity between stem cells from human exfoliated deciduous teeth and dental pulp stem cells].

OBJECTIVE: To compare the osteogenic differentiation potential and osteoclast capacity between stem cells from human exfoliated deciduous teeth (SHED) in the physiological root resorption period and dental pulp stem cells (DPSCs). METHODS: SHED and DPSCs were isolated, purified and cultured in vitro. The two stem cells were examined with ALP staining at 14 days and with alizarin red staining at 21 days of osteogenic induction, and the expressions of the genes associated with osteogenesis and osteoclastogenesis were detected using real-time PCR. RESULTS: The isolated SHED and DPSCs both showed an elongate spindle-shaped morphology. After osteogenic induction of the cells, Alizarin red staining visualized a greater number of mineralized nodules in SHED than in DPSCs (P<0.05), and SHED also exhibited a stronger ALP activity than DPSCs (P<0.05). RT-PCR test results showed that the two stem cells expressed RANKL,OCN, ALP, OPG and Runx2 mRNA after osteogenic induction, but the expression levels of Runx2, OCN and ALP were lower in DPSCs than in SHED (P<0.05), and the ratio of RANKL/OPG was significantly higher in SHED (P<0.05). CONCLUSIONS: Compared with DPSCs, SHED has not only the ability of osteogenic differentiation but also an osteoclast capacity, which sheds light on the regulatory role of SHED in physiological root resorption bone remodeling.

In situ plasma fabrication of ceramic-like structure on polymeric implant with enhanced surface hardness, cytocompatibility and antibacterial capability.

Polymeric materials are commonly found in orthopedic implants due to their unique mechanical properties and biocompatibility but the poor surface hardness and bacterial infection hamper many biomedical applications. In this study, a ceramic-like surface structure doped with silver is produced by successive plasma implantation of silicon (Si) and silver (Ag) into the polyamine 66 (PA66) substrate. Not only the surface hardness and elastic modulus are greatly enhanced due to the partial surface carbonization and the ceramic-like structure produced by the reaction between energetic Si and the carbon chain of PA66, but also the antibacterial activity is improved because of the combined effects rendered by Ag and SiC structure. Furthermore, the modified materials which exhibit good cytocompatibility upregulate bone-related genes and proteins expressions of the contacted bone mesenchymal stem cells (BMSCs). For the first time, it explores out that BMSCs osteogenesis on the antibacterial ceramic-like structure is mediated via the iNOS and nNOS signal pathways. The results reveal that in situ plasma fabrication of an antibacterial ceramic-like structure can endow PA66 with excellent surface hardness, cytocompatibility, as well as antibacterial capability.

High glucose microenvironments inhibit the proliferation and migration of bone mesenchymal stem cells by activating GSK3ß.

Diabetes mellitus involves metabolic changes that can impair bone repair. Bone mesenchymal stem cells (BMSCs) play an important role in bone regeneration. However, the bone regeneration ability of BMSCs is inhibited in high glucose microenvironments. It can be speculated that this effect is due to changes in BMSCs' proliferation and migration ability, because the recruitment of factors with an adequate number of MSCs and the microenvironment around the site of bone injury are required for effective bone repair. Recent genetic evidence has shown that the Cyclin D1 and the CXC receptor 4 (CXCR-4) play important roles in the proliferation and migration of BMSCs. In this study we determined the specific role of glycogen synthase kinase-3ß (GSK3ß) in the proliferation and migration of BMSCs in high glucose microenvironments. The proliferation and migration ability of BMSCs were suppressed under high glucose conditions. We showed that high glucose activates GSK3ß but suppresses CXCR-4, ß-catenin, LEF-1, and cyclin D1. Inhibition of GSK3ß by LiCl led to increased levels of ß-catenin, LEF-1, cyclin D1, and CXCR-4 expression. Our data indicate that GSK3ß plays an important role in regulating the proliferation and migration of BMSCs by inhibiting cyclin D1 and CXCR-4 under high glucose conditions.

Upregulation of BMSCs osteogenesis by positively-charged tertiary amines on polymeric implants via charge/iNOS signaling pathway.

Positively-charged surfaces on implants have a similar potential to upregulate osteogenesis of bone marrow-derived mesenchymal stem cells (BMSCs) as electromagnetic therapy approved for bone regeneration. Generally, their osteogenesis functions are generally considered to stem from the charge-induced adhesion of extracellular matrix (ECM) proteins without exploring the underlying surface charge/cell signaling molecule pathways. Herein, a positively-charged surface with controllable tertiary amines is produced on a polymer implant by plasma surface modification. In addition to inhibiting the TNF-α expression, the positively-charged surface with tertiary amines exhibits excellent cytocompatibility as well as remarkably upregulated osteogenesis-related gene/protein expressions and calcification of the contacted BMSCs. Stimulated by the charged surface, these BMSCs display high iNOS expressions among the three NOS isoforms. Meanwhile, downregulation of the iNOS by L-Can or siRNA inhibit osteogenic differentiation in the BMSCs. These findings suggest that a positively-charged surface with tertiary amines induces osteogenesis of BMSCs via the surface charge/iNOS signaling pathway in addition to elevated ECM protein adhesion. Therefore, creating a positively-charged surface with tertiary amines is a promising approach to promote osseointegration with bone tissues.

Antibacterial and osteoinductive capability of orthopedic materials via cation-π interaction mediated positive charge.

Both implant centered infection and deficient osteoinduction are pivotal issues for orthopedic implants in early and long-term osseointegration, but constructing a functional bio-interface that can overcome these two problems is highly challenging. Our study reveals that a bio-interface with promoted positive charges plays an active role in simultaneously enhancing the antibacterial and osteoinductive capability of orthopedic implants. The positively charged bio-interface is fabricated by a simple dipping method, in which the cationic polymer (polyhexamethylene biguanidine, PHMB) is immobilized in the conjugated polydopamine coating. Mediated by the cation-π interaction, the immobilized PHMB elevates the surface potential resulting in excellent antibacterial efficacy corresponding to 5 ppm of free PHMB. The materials exhibit far better cytocompatibility than free PHMB at the dose which kills over 50% of the cells. Most importantly, the cationic surface can function as a bioelectrical microenvironment to guide bone mesenchymal stem cells and consequently, enhanced cellular viability and proliferation together with upregulated osteogenesis are achieved. The cation-π interaction mediated cationic surface overcomes the disadvantages plaguing the immobilized cationic antibacterial compounds prepared by other methods and is applicable to different types of biomedical materials requiring antibacterial and osteoinductive bio-interfaces.

Effects of plasma-generated nitrogen functionalities on the upregulation of osteogenesis of bone marrow-derived mesenchymal stem cells.

Because of the complex plasma reactions and chemical structures of polymers, it is difficult to construct nitrogen functionalities controllably by plasma technology to attain the desirable biological outcome and hence, their effects on bone cells are sometimes ambiguous and even contradictory. In this study, argon plasma treatment is utilized to convert complex molecular chains into a pyrolytic carbon structure which possesses excellent cytocompatibility. The pyrolytic carbon then serves as a platform to prepare the desired nitrogen functionalities by nitrogen and hydrogen plasma immersion ion implantation. Primary, secondary, and tertiary amine groups can be produced selectively thus minimizing the chemical complexity and creation of multiple types of nitrogen functional groups that are often obtained by other fabrication methods. As a result of the excellent control of the nitrogen functionalities rendered by this plasma technique, the effects of individual nitrogen functionalities on the cytocompatibility and upregulation of bone marrow-derived mesenchymal stem cell (BMSC) osteogenesis can be investigated systematically. The tertiary amine functionalities exhibit the optimal efficiency pertaining to the modulation of the biological response, enhancement of osteogenesis related gene/protein expression, and calcification of the contacted BMSCs. Our results demonstrate that simple plasma technology can be conveniently employed to create the desirable nitrogen functionalities on orthopedic polymers to facilitate osseointegration and mitigate foreign body reactions.

Mesenchymal stem cells prevent hypertrophic scar formation via inflammatory regulation when undergoing apoptosis.

The cutaneous wound-healing process can lead to hypertrophic scar formation, during which exaggerated inflammation has been demonstrated to have an important role. Therefore, an exploration of strategies designed to regulate this inflammatory process is warranted. Mesenchymal stem cells (MSCs) have recently been demonstrated to regulate inflammation in various diseases. In this regard, using a rabbit model, we locally injected human mesenchymal stem cells (hMSCs) derived from bone marrow to treat hypertrophic scar formation, and explored their underlying mechanisms. We found that hMSC therapy efficiently regulated inflammation and prevented scar formation. We attributed the therapeutic effects of hMSCs to their secretion of an anti-inflammatory protein, TNF-alpha-stimulated gene/protein 6 (TSG-6). Unexpectedly, after injection, the number of surviving hMSCs decreased markedly and the hMSCs underwent extensive apoptosis, which was demonstrated to promote their secretion of TSG-6, partially through the activation of caspase-3. Moreover, H2O2-induced apoptotic hMSCs showed higher inflammatory regulatory abilities. The inhibition of caspase-3 decreased the inflammatory regulatory abilities of hMSCs and attenuated their therapeutic effects. Our results demonstrate that hMSCs can efficiently prevent hypertrophic scar formation via inflammatory regulation. In addition, we found that apoptosis has an important role in the activation of the inflammatory regulatory abilities of hMSCs.

Electrospun tubular scaffold with circumferentially aligned nanofibers for regulating smooth muscle cell growth.

Simulation for the smooth muscle layer of blood vessel plays a key role in tubular tissue engineering. However, fabrication of biocompatible tube with defined inner nano/micro-structure remains a challenge. Here, we show that a biocompatible polymer tube from poly(l-lactide) (PLLA) and polydimethylsiloxane (PDMS) can be prepared by using electrospinning technique, with assistance of rotating collector and parallel auxiliary electrode. The tube has circumferentially aligned PLLA fibers in the inner surface for cell growth regulation and has a PDMS coating for better compressive property. MTT assay showed the composite PLLA/PDMS tube was suitable for various cells growth. In vitro smooth muscle cells (SMCs) cultured in the tube showed that the aligned PLLA fibers could induce SMCs' orientation, and different expression of α-SMA and OPN genes were observed on the aligned and random PLLA fibers, respectively. The successful fabrication of composite PLLA/PDMS tubular scaffold for regulating smooth muscle cells outgrowth has important implications for tissue-engineered blood vessels.

Scaffold-free cell pellet transplantations can be applied to periodontal regeneration.

Cell transplantation has emerged as a novel therapeutic strategy for periodontitis, and the adoption of cell pellet offers advantages by secreting abundant extracellular matrix (ECM) and eliminating the adverse effect of cell carriers. This study aimed to fabricate scaffold-free periodontal ligament stem cell (PDLSC) pellets (MUCPs) and to evaluate their regeneration potential. We constructed monolayer cell pellets (MCPs) by fabricating and culturing multilayered cell sheets (MUCS) and constructed MUCPs from the MUCS. Immunochemistry, scanning electron microscope, real-time PCR, and Western blot analysis showed higher levels of COL-I, COL-III, fibronectin, and laminin in the MUCPs. Furthermore, the massive increase in ECM secretion improved cell adhesion, migration, and proliferation. Finally, upon transplantation into the omentum sac and periodontal defects, all the transplants formed regular aligned cementum/PDL-like complex, but the mineral deposit and fiber alignment were more obvious in the MUCPs than in the MCPs. Altogether, our results suggest that MUCPs may be a promising alternative to periodontal repair for future clinical application.

Hetero-epitaxy of anisotropic polycaprolactone films for the guidance of smooth muscle cell growth.

An anisotropic biocompatible composite PCL-PTFE film was used to guide smooth muscle cell outgrowth along defined directions.